期刊
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
卷 48, 期 4, 页码 -出版社
WILEY
DOI: 10.1111/nan.12793
关键词
Alzheimer's disease; dentate nucleus; frontotemporal dementia; hnRNP K
资金
- Alzheimer's Society and Guarantors of Brain - Medical Research Council [MR/M008606/1, MR/S006508/1]
- UK Motor Neurone Disease Association
- Rosetrees Trust
- UCLH NIHR Biomedical Research Centre
- Alzheimer's Research UK senior fellowship
- Eisai
- Wolfson Foundation
- Reta Lila Weston Institute for Neurological Studies
This study reveals that nuclear depletion and cytoplasmic mislocalisation of hnRNP K are common neuropathological features in FTLD and elderly control brain. Furthermore, the dentate nucleus of the cerebellum is also vulnerable to hnRNP K mislocalisation. The findings suggest that hnRNP K dysfunction may have broader relevance to neurodegeneration and ageing.
Nuclear depletion and cytoplasmic mislocalisation of the RNA-binding protein heterogeneous ribonucleoprotein K (hnRNP K) within pyramidal neurons of the frontal cortex have been shown to be a common neuropathological feature in frontotemporal lobar degeneration (FTLD) and elderly control brain. Here, we describe a second neuronal subtype vulnerable to mislocalisation within the dentate nucleus of the cerebellum. In contrast to neurons within the cerebellar cortex that typically exhibited normal, nuclear staining, many neurons of the dentate nucleus exhibited striking mislocalisation of hnRNP K to the cytoplasm within neurodegenerative disease brain. Mislocalisation frequency in this region was found to be significantly higher in both FTLD-TDP A and Alzheimer's disease (AD) brain than in age-matched controls. However, within control (but not disease) subjects, mislocalisation frequency was significantly associated with age-at-death with more elderly controls typically exhibiting greater levels of the pathology. This study provides further evidence for hnRNP K mislocalisation being a more anatomically diverse pathology than previously thought and suggests that potential dysfunction of the protein may be more broadly relevant to the fields of neurodegeneration and ageing.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据